While MHC-restricted T helper cell interactions with macrophages and B cells have been well documented in recent years, very little is known about T-T cell interactions between T cell subpopulations. Recently, we isolated and characterized several self-Ia reactive (autoreactive) Lyt 1+2-, L3T4+, Ia- T cell clones from normal, unimmunized DBA/2 mice and used them to analyze the T-T network concept postulated to exist in the normal immune system. These studies led to an interesting and unique finding that Lyt 1+ but not Lyt 2+ T cells isolated from normal DBA/2 mice proliferate strongly and directly in response to autoreactive T cells. Further studies will be carried out to address the following specific aims: (1) Nature and characteristics of the T-T interaction between antiautoreactive Lyt 1+2- cells and autoreactive T cells. 2) Do antiautoreactive Lyt 1+2- cells have receptors with internal images of Ia molecules? 3) What is the functional significance of the T-T interaction and possible role of T cells bearing internal images of Ia on their receptors, in the generation of T-helper cell repertoire? The above mentioned studies will be carried out by using autoreactive T cell clones and hybridomas which have been developed and well characterized. Similar attempts will be made to develop anti-autoreactive Lyt 1+2- T cell clones and hybridomas. Attempts will be made to develop mAbs to the autoreactive T cells and determine the nature of antigenic determinant recognized by the Lyt 1+2- T cells. Monoclonal antibodies will also be developed against the antiautoreactive T cell receptor and these along will mAbs to autoreactive T cells will be used in vitro and in vivo to understand the functional significance of the T-T interaction and its relation to the generation of the T-helper cell repertoire. It has been suggested that autoreactive T cells and T cell immune networks play an important role in maintaining normal immune system homeostasis and any perturbation in these cells could lead to disturbed immuno-regulation and development of autoimmune or lymphoproliferative diseases and neoplasia. Thus, the present investigation would help in understanding the network regulation among T cells and its role in autoimmune or lymphoproliferative disorders and in neoplasia.